Study finds mutations in lung cancer DNA

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The largest and most comprehensive genomic study of the most common kind of lung cancer has revealed an exhaustive library of mutations carried by tumors, providing information that could help guide scientists’ efforts to devise new treatments.

A large team, led in part by researchers from the Broad Institute and Dana-Farber Cancer Institute, analyzed tumors from 230 patients with lung adenocarcinoma, the leading cause of cancer death worldwide. They identified the top 18 gene mutations in a paper published Wednesday in the journal Nature.

In some ways, the results are not a surprise: many of the common genetic mutations were already known in lung cancer, and several drugs already exist to target some of them or are in development. But the new work underlines the idea that cancers may be caused by very different genetic mutations that have complementary effects: nearly three-quarters of the lung cancer in the study involved genetic alterations that flip one particular cell signaling pathway into overdrive. There are targeted drugs available or in development that might now be applied to this broad swath of patients.

In addition, scientists said that understanding the fine details of all the DNA mutations present in tumors are crucial because cancers almost inevitably develop resistance to drugs.

“In the end, we’re not likely going to be able to cure with single drugs; we’re going to need combinations of drugs, and those combinations will need to act through multiple pathways,” said Dr. Matthew Meyerson, a professor of pathology at Dana-Farber who led the work. Meyerson is a founder of Foundation Medicine, a Cambridge-based company focused on using genetic profiles of cancer to guide treatment.

The study is the latest publication from the Cancer Genome Atlas, a federally funded effort to document the genetic mutations that drive different types of cancer.

“What people have to understand is this is an unheard of effort; if you think back 10 years ago, the fact you could even do this work is just mind-boggling in terms of complexity,” said Dr. Thomas Lynch, director of the Yale Cancer Center, who was not involved in the study.

What is likely, Lynch said, is that a small subset of cancers in different organs will share genetic drivers and knowing this information across many different cancers will provide different ways to develop and test drugs.